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Angiotensin receptor blockers for the treatment of high blood pressure

A class of drugs called angiotensin receptor blockers (ARBs) is commonly used to lower high blood pressure. This class includes drugs such as losartan (brand name: Cozaar), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), telmisartan (Micardis) and valsartan (Diovan). We asked how much this class of drugs lowers blood pressure and whether there is a difference between individual drugs within the class. The available scientific literature was searched to find all trials that had assessed these questions.

We found 46 trials that randomly assigned participants to take either an ARB or an inert substance (placebo). These trials evaluated the BP lowering ability of 9 different ARBs in 13 451 participants altogether. The trials followed participants for only 7 weeks (though people are typically expected to take anti-hypertension drugs for the rest of their lives). The blood pressure lowering effect was modest. There was an 8-point reduction in the upper number that signifies the systolic pressure and a 5-point reduction in the lower number that signifies the diastolic pressure. Most of the blood pressure lowering effect (about 70%) can be achieved with the lowest recommended dose of the drugs. No ARB appears to be any better or worse than others in terms of blood pressure lowering ability.

Almost all of the trials in this review were funded by companies that make ARBs and serious adverse effects were not reported by the authors of half of these trials. This could mean that the drug companies are withholding unfavorable findings related to their drugs. Due to incomplete reporting of the number of participants who dropped out of the trials due to adverse drug reactions, as well as the short duration of these trials, this review could not provide a good estimate of the harms associated with this class of drugs. Prescribing the least expensive ARBs in lower doses will lead to substantial cost savings, and possibly a reduction in dose-related adverse events.

Authors' conclusions:

The evidence from this review suggests that there are no clinically meaningful BP lowering differences between available ARBs. The BP lowering effect of ARBs is modest and similar to ACE inhibitors as a class; the magnitude of average trough BP lowering for ARBs at maximum recommended doses and above is -8/-5 mmHg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses. The review did not provide a good estimate of the incidence of harms associated with ARBs because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

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Background:

Angiotensin receptor blockers (ARBs) are widely prescribed for hypertension so it is essential to determine and compare their effects on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAE).

Objectives:

To quantify the dose-related systolic and/or diastolic BP lowering efficacy of ARBs versus placebo in the treatment of primary hypertension.

Search strategy:

We searched CENTRAL (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to February 2007), EMBASE (1988 to February 2007) and reference lists of articles.

Selection criteria:

Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of fixed-dose monotherapy with an ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension.

Data collection and analysis:

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. WDAE information was collected from the trials.

Main results:

Forty six RCTs evaluated the dose-related trough BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 156/101 mm Hg. The data do not suggest that any one ARB is better or worse at lowering BP. A dose of 1/8 or 1/4 of the manufacturers’ maximum recommended daily dose (Max) achieved a BP lowering effect that was 60 to 70% of the BP lowering effect of Max. A dose of 1/2 Max achieved a BP lowering effect that was 80% of Max. ARB doses above Max did not significantly lower BP more than Max. Due to evidence of publication bias, the largest trials provide the best estimate of the trough BP lowering efficacy for ARBs as a class of drugs: -8 mm Hg for SBP and -5 mm Hg for DBP. ARBs reduced BP measured 1 to 12 hours after the dose by about 12/7 mm Hg.

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